2-232087546-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_152383.5(DIS3L2):c.426C>T(p.Pro142Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,613,892 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 19 hom., cov: 31)

Exomes 𝑓: 0.014 ( 194 hom. )

Consequence

DIS3L2
NM_152383.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.54

Variant links:

Genes affected

DIS3L2 (HGNC:28648): (DIS3 like 3'-5' exoribonuclease 2) The protein encoded by this gene is similar in sequence to 3'/5' exonucleolytic subunits of the RNA exosome. The exosome is a large multimeric ribonucleotide complex responsible for degrading various RNA substrates. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Mar 2012]

DIS3L2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 2-232087546-C-T is Benign according to our data. Variant chr2-232087546-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232087546-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-4.54 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1720/152042) while in subpopulation NFE AF= 0.0164 (1117/67982). AF 95% confidence interval is 0.0156. There are 19 homozygotes in gnomad4. There are 859 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIS3L2	NM_152383.5 link	c.426C>T	p.Pro142Pro	synonymous_variant	Exon 6 of 21	ENST00000325385.12	NP_689596.4	Q8IYB7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIS3L2	ENST00000325385.12 link	c.426C>T	p.Pro142Pro	synonymous_variant	Exon 6 of 21	5	NM_152383.5	ENSP00000315569.7		Q8IYB7-1

Frequencies

GnomAD3 genomes

AF:

0.0113

AC:

1723

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00747

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00291

Gnomad FIN

AF:

0.0278

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.0106

GnomAD3 exomes

AF:

0.0113

AC:

2817

AN:

249502

Hom.:

AF XY:

0.0111

AC XY:

1500

AN XY:

135348

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00478

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00228

Gnomad SAS exome

AF:

0.00438

Gnomad FIN exome

AF:

0.0284

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

AF:

0.0138

AC:

20131

AN:

1461850

Hom.:

194

Cov.:

AF XY:

0.0135

AC XY:

9785

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00438

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00222

Gnomad4 SAS exome

AF:

0.00434

Gnomad4 FIN exome

AF:

0.0288

Gnomad4 NFE exome

AF:

0.0151

Gnomad4 OTH exome

AF:

0.0128

GnomAD4 genome

AF:

0.0113

AC:

1720

AN:

152042

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

859

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00746

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0278

Gnomad4 NFE

AF:

0.0164

Gnomad4 OTH

AF:

0.00999

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.00881

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0143

EpiControl

AF:

0.0129

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Perlman syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 23, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.32

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over